Guillain-Barré Syndrome

I have been talking to people for more than a decade about their experiences with Transverse Myelitis and the other neuroimmunologic disorders.  One of the most frequently discussed topics is the difficulty in diagnosing TM.  The challenges people experience in receiving an accurate diagnosis has been chronicled repeatedly in the In Their Own Words articles.  The Johns Hopkins TM Center has devoted a tremendous amount of time, effort and resources into developing diagnostic criteria for TM and disseminating this information to the medical community.  The diagnostic criteria and algorithm have been published in a number of articles and is presented both on the Johns Hopkins TM Center and TMA web sites.

The TM diagnosis remains a challenge for the medical community.  A part of the challenge concerns the fact that there are many different diseases and disorders that present with very similar symptoms as are associated with TM.  The TMA Survey Project was initiated in 1997 and the survey administration was completed in 2004.  There were 815 respondents to the survey covering both pediatric and adult cases of Transverse Myelitis.  In the survey we asked people to identify the first diagnosis they received.  Of the 815 respondents, 782 provided an answer to this question.  There were 458 (58%) who were told they had TM as their first diagnosis.  There were 67 (9%) who were told they had MS, 64 (8%) were told they had Guillain-Barré, 39 (5%) were given no diagnosis and 32 (4%) were told they had some type of structural problem.  There were numerous other diagnoses (16%) given to the respondents; the total number in each category being relatively small in comparison to the responses reported.  The other category included such diagnoses as vascular myelopathies or spinal strokes, psychosomatic or hysterical paralysis, ADEM, Devic’s disease, and spinal cord tumors.

As I continue to learn about the neuroimmunologic diseases, I develop a greater appreciation for the difficulties clinicians face in making the TM diagnosis, and this is particularly the case for physicians in general practice who very rarely if ever see a case of this disorder in their practice.  What follows is a fact sheet about Guillain-Barré that is published by the National Institute of Neurological Disorders and Stroke (National Institutes of Health).  The fact sheet provides an excellent description of Guillain-Barré and also offers a demonstration of the confusing issues which clinicians must address in making an accurate diagnosis from among these neuroimmunologic diseases.  In your consideration of these diagnostic challenges, it is important to bear in mind that Transverse Myelitis involves an inflammatory attack in the central nervous system while Guillain-Barré involves the peripheral nervous system.

Guillain-Barré Syndrome Fact Sheet

What is Guillain-Barré syndrome?
Guillain-Barré (ghee-yan bah-ray) syndrome is a disorder in which the body's immune system attacks part of the peripheral nervous system. The first symptoms of this disorder include varying degrees of weakness or tingling sensations in the legs. In many instances the weakness and abnormal sensations spread to the arms and upper body. These symptoms can increase in intensity until certain muscles cannot be used at all and, when severe, the patient is almost totally paralyzed. In these cases the disorder is life threatening - potentially interfering with breathing and, at times, with blood pressure or heart rate - and is considered a medical emergency. Such a patient is often put on a respirator to assist with breathing and is watched closely for problems such as an abnormal heart beat, infections, blood clots, and high or low blood pressure. Most patients, however, recover from even the most severe cases of Guillain-Barré syndrome, although some continue to have a certain degree of weakness.

Guillain-Barré syndrome can affect anybody. It can strike at any age and both sexes are equally prone to the disorder. The syndrome is rare, however, afflicting only about one person in 100,000. Usually Guillain-Barré occurs a few days or weeks after the patient has had symptoms of a respiratory or gastrointestinal viral infection. Occasionally surgery or vaccinations will trigger the syndrome.

After the first clinical manifestations of the disease, the symptoms can progress over the course of hours, days, or weeks. Most people reach the stage of greatest weakness within the first 2 weeks after symptoms appear, and by the third week of the illness 90 percent of all patients are at their weakest.

What causes Guillain-Barré syndrome?
No one yet knows why Guillain-Barré - which is not contagious - strikes some people and not others. Nor does anyone know exactly what sets the disease in motion.

What scientists do know is that the body's immune system begins to attack the body itself, causing what is known as an autoimmune disease. Usually the cells of the immune system attack only foreign material and invading organisms. In Guillain-Barré syndrome, however, the immune system starts to destroy the myelin sheath that surrounds the axons of many peripheral nerves, or even the axons themselves (axons are long, thin extensions of the nerve cells; they carry nerve signals). The myelin sheath surrounding the axon speeds up the transmission of nerve signals and allows the transmission of signals over long distances.

In diseases in which the peripheral nerves' myelin sheaths are injured or degraded, the nerves cannot transmit signals efficiently. That is why the muscles begin to lose their ability to respond to the brain's commands, commands that must be carried through the nerve network. The brain also receives fewer sensory signals from the rest of the body, resulting in an inability to feel textures, heat, pain, and other sensations. Alternately, the brain may receive inappropriate signals that result in tingling, "crawling-skin," or painful sensations. Because the signals to and from the arms and legs must travel the longest distances they are most vulnerable to interruption. Therefore, muscle weakness and tingling sensations usually first appear in the hands and feet and progress upwards.

When Guillain-Barré is preceded by a viral or bacterial infection, it is possible that the virus has changed the nature of cells in the nervous system so that the immune system treats them as foreign cells. It is also possible that the virus makes the immune system itself less discriminating about what cells it recognizes as its own, allowing some of the immune cells, such as certain kinds of lymphocytes and macrophages, to attack the myelin. Sensitized T lymphocytes cooperate with B lymphocytes to produce antibodies against components of the myelin sheath and may contribute to destruction of the myelin. Scientists are investigating these and other possibilities to find why the immune system goes awry in Guillain-Barré syndrome and other autoimmune diseases. The cause and course of Guillain-Barré syndrome is an active area of neurological investigation, incorporating the cooperative efforts of neurological scientists, immunologists, and virologists.

How is Guillain-Barré syndrome diagnosed?
Guillain-Barré is called a syndrome rather than a disease because it is not clear that a specific disease-causing agent is involved. A syndrome is a medical condition characterized by a collection of symptoms (what the patient feels) and signs (what a doctor can observe or measure). The signs and symptoms of the syndrome can be quite varied, so doctors may, on rare occasions, find it difficult to diagnose Guillain-Barré in its earliest stages.
Several disorders have symptoms similar to those found in Guillain-Barré, so doctors examine and question patients carefully before making a diagnosis. Collectively, the signs and symptoms form a certain pattern that helps doctors differentiate Guillain-Barré from other disorders. For example, physicians will note whether the symptoms appear on both sides of the body (most common in Guillain-Barré) and the quickness with which the symptoms appear (in other disorders, muscle weakness may progress over months rather than days or weeks). In Guillain-Barré, reflexes such as knee jerks are usually lost. Because the signals traveling along the nerve are slower, a nerve conduction velocity (NCV) test can give a doctor clues to aid the diagnosis. In Guillain-Barré patients, the cerebrospinal fluid that bathes the spinal cord and brain contains more protein than usual. Therefore a physician may decide to perform a spinal tap, a procedure in which the doctor inserts a needle into the patient's lower back to draw cerebrospinal fluid from the spinal column.

How is Guillain-Barré treated?
There is no known cure for Guillain-Barré syndrome. However, there are therapies that lessen the severity of the illness and accelerate the recovery in most patients. There are also a number of ways to treat the complications of the disease.

Currently, plasma exchange (sometimes called plasmapheresis) and high-dose immunoglobulin therapy are used. Both of them are equally effective, but immunoglobulin is easier to administer. Plasma exchange is a method by which whole blood is removed from the body and processed so that the red and white blood cells are separated from the plasma, or liquid portion of the blood. The blood cells are then returned to the patient without the plasma, which the body quickly replaces. Scientists still don't know exactly why plasma exchange works, but the technique seems to reduce the severity and duration of the Guillain-Barré episode. This may be because the plasma portion of the blood contains elements of the immune system that may be toxic to the myelin.

In high-dose immunoglobulin therapy, doctors give intravenous injections of the proteins that, in small quantities, the immune system uses naturally to attack invading organisms. Investigators have found that giving high doses of these immunoglobulins, derived from a pool of thousands of normal donors, to Guillain-Barré patients can lessen the immune attack on the nervous system. Investigators don't know why or how this works, although several hypotheses have been proposed.

The use of steroid hormones has also been tried as a way to reduce the severity of Guillain-Barré, but controlled clinical trials have demonstrated that this treatment not only is not effective but may even have a deleterious effect on the disease.

The most critical part of the treatment for this syndrome consists of keeping the patient's body functioning during recovery of the nervous system. This can sometimes require placing the patient on a respirator, a heart monitor, or other machines that assist body function. The need for this sophisticated machinery is one reason why Guillain-Barré syndrome patients are usually treated in hospitals, often in an intensive care ward. In the hospital, doctors can also look for and treat the many problems that can afflict any paralyzed patient - complications such as pneumonia or bed sores.

Often, even before recovery begins, caregivers may be instructed to manually move the patient's limbs to help keep the muscles flexible and strong. Later, as the patient begins to recover limb control, physical therapy begins. Carefully planned clinical trials of new and experimental therapies are the key to improving the treatment of patients with Guillain-Barré syndrome. Such clinical trials begin with the research of basic and clinical scientists who, working with clinicians, identify new approaches to treating patients with the disease.

What is the long-term outlook for those with Guillain-Barré syndrome?
Guillain-Barré syndrome can be a devastating disorder because of its sudden and unexpected onset. In addition, recovery is not necessarily quick. As noted above, patients usually reach the point of greatest weakness or paralysis days or weeks after the first symptoms occur. Symptoms then stabilize at this level for a period of days, weeks, or, sometimes, months. The recovery period may be as little as a few weeks or as long as a few years. About 30 percent of those with Guillain-Barré still have a residual weakness after 3 years. About 3 percent may suffer a relapse of muscle weakness and tingling sensations many years after the initial attack.

Guillain-Barré syndrome patients face not only physical difficulties, but emotionally painful periods as well. It is often extremely difficult for patients to adjust to sudden paralysis and dependence on others for help with routine daily activities. Patients sometimes need psychological counseling to help them adapt.

What research is being done?
Scientists are concentrating on finding new treatments and refining existing ones. Scientists are also looking at the workings of the immune system to find which cells are responsible for beginning and carrying out the attack on the nervous system. The fact that so many cases of Guillain-Barré begin after a viral or bacterial infection suggests that certain characteristics of some viruses and bacteria may activate the immune system inappropriately. Investigators are searching for those characteristics. Certain proteins or peptides in viruses and bacteria may be the same as those found in myelin, and the generation of antibodies to neutralize the invading viruses or bacteria could trigger the attack on the myelin sheath. As noted previously, neurological scientists, immunologists, virologists, and pharmacologists are all working collaboratively to learn how to prevent this disorder and to make better therapies available when it strikes.

Where can I get more information?
For more information on neurological disorders or research programs funded by the National Institute of Neurological Disorders and Stroke, contact the Institute's Brain Resources and Information Network (BRAIN) at:

BRAIN
P.O. Box 5801
Bethesda, MD 20824
(800) 352-9424
www.ninds.nih.gov

Information also is available from the following organizations:

GBS/CIDP Foundation International
P.O. Box 262
Wynnewood, PA 19096
info[AT SIGN]gbsfi.com  http://gbsifi.com
Tel: 610-667-0131
Fax: 610-667-7036

"Guillain-Barre Syndrome Fact Sheet", NINDS.  NIH Publication No. 05-2902
Last updated December 08, 2005

Prepared and Reprinted with Permission by: Office of Communications and Public Liaison; National Institute of Neurological Disorders and Stroke; National Institutes of Health; Bethesda, MD 20892

NINDS health-related material is provided for information purposes only and does not necessarily represent endorsement by or an official position of the National Institute of Neurological Disorders and Stroke or any other Federal agency. Advice on the treatment or care of an individual patient should be obtained through consultation with a physician who has examined that patient or is familiar with that patient's medical history.